The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a $60 million, multi-site, longitudinal, prospective, naturalistic study of individuals with normal cognitive aging, mild cognitive impairment (MCI), and early Alzheimer's disease (AD) to facilitate the scientific evaluation of neuroimaging and other markers for the onset and progression of MCI and AD. Tests of cognitive functioning provide the benchmark for comparison in ADNI. A major limitation of the ADNI project is that modern psychometric analyses are not applied. Our group of investigators from the University of Washington, the University of California Davis, Washington University in St. Louis, and the Hebrew Rehabilitation Center for the Aged in Boston intend to address this limitation to determine those methods best able to detect and measure important changes over time. We will combine analyses of ADNI data with analyses of data from the Subcortical Ischemic Vascular Disease Program Project Grant (Helena Chui, PI) to pursue the following specific aims: Aim 1. Develop strategies for measuring change over time in subjects with normal aging, MCI, and AD using modern psychometric methods applied to neuropsychological data from ADNI and SIVD PPG. Aim 2. Evaluate modern psychometric methods for measuring change over time, and compare with conventional analyses using simulated and real data. Aim 3. Develop and evaluate strategies for combining neuropsychological, neuroimaging, and biomarker data into composite outcomes for randomized controlled trials (RCTs) of interventions to prevent and treat MCI and AD. Aim 4. Develop clinically useful score reports for the Uniform Data Set (UDS) to summarize general cognition, memory, and executive functioning, accounting for DIP and measurement error. We will test several hypotheses and hope to illustrate statistical techniques for optimizing the robustness of the psychometric data that will be collected in future clinical trials, whether alone or in conjunction with imaging. [unreadable] [unreadable] [unreadable]